TRYMO (Colloidal Bismuth Subtitrate) is the colloidal bismuth salt of citric add. it is effective in alleviating symptoms in patients with gastric or duodenal ulcer. It also accelerates the healing of gastric and duodenal ulcers. The mode of action is distinct from that of other anti-ulcer drugs including H2-receptor antagonists.

The following pharmacological actions were observed in expenmental animals:

1. Bismuth oxide precipitated from CBS by the action of acid in the stomach, forms a tenacious layer upon the digestive mucosa.

2. By fixing chloride ion and formation of insoluble bismuth oxychloride, diffusion of bismuth ion into the circulation is prevented and thereby CBS toxicity is eliminated.

3. Bismuth ions inhibit the growth of Enterococci, Staphylococci. Pseudomonas, and thereby alter the microbial flora in the G.l. tract

4. Bismuth ions increase the secretion of mucus, which inhibits the activity of hydrochloric add and pepsin.

5. It exerts an anti-ulcer effect in rats and guinea pigs in which ulcers are induced by various means.

6. In-vitro studies have shown that CBS together with gastric glycoproteins forms a complex’, which markedly retards the migration of H* ions. The formation of this layer at the ulcer site acts as a diffusion barrier to hydrochloric acid.

The usual postulates for pharmacological actions in human are:

At pH less than 5, TRYMO forms a predpitate of bismuth oxychloride and bismuth citrate. By chelate formation, protein degradation products together with the precipitate obtained from TRYMO form an insoluble layer at the ulcer site.

TRYMO also binds with mucus forming a glycoprotein-bismuth complex providing a diffusion barrier to HCL without affecting the ion change properties of the mucus.

TRYMO enhances the increase of macrophages, which may assist early healing of the damaged mucosa.

TRYMO has a direct bactericidal effect on Helicobacter pylori: vacuolisation occurred within the bacteria, resulting in fragmented cell walk and. in some cases, complete condensation of the cell contents. Bismuth was seen deposited in aggregates on the surface and within the bacteria.

TRYMO has littie effect on the acidity of gastric fluid.

PHARMACOKINETICS

Absorption: The action of TRYMO is fully dependent on the local action at the ulcer site. However, very small amounts of bismuth are absorbed from the G.l. tract. The absorption is initially dose-dependent and reaches the dynamic equilibrium (steady state level) after 4 weeks of administration with the normal dosage of 480 mg/day and no further rise in blood or urine levels at 5 and 6 weeks. The mean concentration was only 7 ng/ml, which is far below the alerting levels of 50 to 100 ng/ml.

Distribution: Studies carried out in animals show that most of the absorbed

bismuth reaches the kidneys with only trace amounts In other organs. In dogs with experimental ulcers, CBS was given for 3 weeks in doses 20 times as those recommended for man and the tissues were examined for bismuth concentrations by optical density measurements. The kidneys contained 34.3 ppm of bismuth and only traces in other organs, namely, stomach 4.3 ppm, liver 2.1 ppm. Spleen 0.7 ppm, mesenteric lymph nodes 1.6 ppm, blood less than 0.5 ppm. Human data on tissue distribution of TRYMO is not yet available. Bioavailability is not applicable since TRYMO acts locally.

Excretion: Most of the bismuth in TRYMO is excreted in the faeces as bismuth sulphate. The very small amount of bismuth, which may be absorbed, k eliminated via the kidneys. This excretion Is at a slow rate of about 2.6 % per day; mean urinary excretion levels were In the range of 411 to 639 mcg/24 hours during 4-6 weeks treatment period. Therefore a wash out period of about 2 months is required after each course of TRYMO before considering afresh treatment with TRYMO.

Colloidal bismuth subcitrate (Trymo) can be used as triple therapy (with metronidazole and either tetracycline or amoxicillin) to eradicate Helicobacter pylori.

CONTRAINDICATIONS

Severe renal insufficiency. TRYMO is not recommended during pregnancy and lactation. TRYMO is not indicated in children.

DOSAGE AND ADMINISTRATION

TRYMO, two tablets twice a day on an empty stomach, half an hour before meals to be swallowed whole and not chewed. TRYMO should be used a initially for a period of 4 weeks and if required up to a maximum of 8 weeks. TRYMO should not be used as maintenance therapy after the maximum ) period of 8 week is over. If a new course of TRYMO tablets is contemplated.

it is advised to give a gap of at least 8 weeks before the therapy is restarted.

When used as a part of triple therapy. 1 tablet of Trymo is given 4 times daily for 2 weeks.

ADVERSE DRUG REACTIONS

Nausea, vomiting and diarrhoea have been occasionally reported with the use of TRYMO. Headache and giddiness have been mentioned by some investigators. Darkening of the stools is due to the excretion of bismuth sulphide. Inform your physician the unwanted effects afterusing.

PRECAUTIONS

Though no reports of bismuth encephalopathy following the use of colloidal bismuth subcitrate in the recommended doses have been made, the possibility should be kept in mind and overdosage should be avoided. For the same reason, long-term usage (maintenance therapy) is not recommended.

There Is insufficient information available on use of colloidal bismuth subettiate during pregnancy and lactation.

The product should be consumed before the expiry date.

DRUG INTERACTIONS

The absorption of iron, calcium or tetracycline may be reduced following theirconcomitant administration with TRYMO.

Antacids or milk given along with TRYMO may form a chelate with and may interfere with the action of colloidal bismuth subcitrate. Thus, it is advised that food or antacids should not be taken within 30 minutes before or after administration of TRYMO.